糖尿病相关最新一篇文章

大猪小猪落玉盘

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, I4 p3 p' ^7 x0 q% R& mIntrauterine growth retardation (IUGR) has been linked to the onset of diseases in adulthood, including type+ q1 l7 j7 O0 g' n8 K7 ~
2 diabetes, and has been proposed to result from altered gene regulation patterns due to epigenetic modifications* B& J+ i5 P) P/ _+ ]
of developmental genes. To determine whether epigenetic modifications may play a role in the development
+ X% d0 F# y/ E6 W9 Sof adult diabetes following IUGR, we used a rodent model of IUGR that expresses lower levels of Pdx1, a$ X& r- z5 x* M: ^+ R8 g& j8 W
pancreatic and duodenal homeobox 1 transcription factor critical for β cell function and development, which, K! W1 N, p2 C; _. ^: N5 ~/ l1 d
develops diabetes in adulthood. We found that expression of Pdx1 was permanently reduced in IUGR β cells% o0 g! G3 ^" p# w9 r8 u# ]# \+ D
and underwent epigenetic modifications throughout development. The fetal IUGR state was characterized by
* r/ l9 Q' O$ s1 _  Dloss of USF-1 binding at the proximal promoter of Pdx1, recruitment of the histone deacetylase 1 (HDAC1) and& I! `  O" |) O3 @2 R
the corepressor Sin3A, and deacetylation of histones H3 and H4. Following birth, histone 3 lysine 4 (H3K4)# u3 o& C9 `$ Z1 a
was demethylated and histone 3 lysine 9 (H3K9) was methylated. During the neonatal period, these epigenetic/ s5 }3 V5 h* d! J
changes and the reduction in Pdx1 expression could be reversed by HDAC inhibition. After the onset of diabetes
. H% m3 d& U+ G. u. y' M: L2 bin adulthood, the CpG island in the proximal promoter was methylated, resulting in permanent silencing, ?7 s/ ~+ @3 ^, s. ]4 ?) ?
of the Pdx1 locus. These results provide insight into the development of type 2 diabetes following IUGR and we
/ O& D) r3 d8 ^) x6 C) \believe they are the first to describe the ontogeny of chromatin remodeling in vivo from the fetus to the onset- `# H. R( J( d: j$ _
of disease in adulthood.6 r# U( h$ u8 q+ ?# q
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cdcliwei

Well done!

xiaomao_zhoubo

支持

jimzhua

谢谢

missyoudad

谢谢分享

w1986725

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